The long-term objective of the Physician-Scientist Award is for the principal investigator to prepare for a career as an independent researcher in the biomedical sciences through five years of basic science training. Phase I will consist of intensive training in molecular and cell biology which will be primarily accomplished through work on a research project in the Laboratory of Cell Biology at Rockefeller University. Specifically, the project will be concerned with characterization of protein components of the nuclear pore complex, an organelle involved in the transport of macromolecules between the nucleus and cytoplasm of eukaryotic cells. Pore complex proteins will be purified by monoclonal antibody affinity chromatography with antibodies found to inhibit macromolecule transport across the nuclear envelope of isolated nuclei. Polyclonal antibodies will be raised against these purified proteins and oligonucleotide probes will be synthesized complementary to the determined amino acid sequences of fragments if these proteins. The polyclonal antibodies and oligonucleotide probes will be used to screen cDNA libraries to islolate clones encoding pore complex proteins. The cDNA clones will be sequenced to obtain the entire amino acid sequences of the pore complex proteins. Such information should provide a better understanding of the role of the nuclear pore complex in the selective transport of macromolecules across the nuclear envelope. In Phase II of the Award, research will be conducted in the Department of Medicine at Cornell University Medical College. Methodology learned during Phase I will be used to characterize membrane bound proteins of hepatocytes or intestinal epithelial cells. Such proteins are involved in physiological functions ranging from billirubin metabolism to ion transport, and these proteins may be defective in various disease states. Characterization of membrane bound proteins of hepatic or intestinal cells at the molecular level should provide a better understanding of their functions in normal physiology and possible dysfunction in disease states.